Breast cancer is the most frequent cause of cancer-related deaths among women in the western world. Among these patients, one of four women dies from breast cancer, despite improvements in diagnosis, surgery, chemotherapy and the new targeted therapies. Death is associated with the metastatic development of the disease. The discovery and characterization of new contributors remain necessary in order to develop appropriate and highly specific treatments targeted to metastasis initiation and progression processes.
During 1997, more than 36 000 new cases of ductal carcinoma in situ (DCIS), representing 17% of all new breast cancers, were diagnosed in the United States. Most of these cases were diagnosed by mammography. High quality mammography is capable of finding a range of asymptomatic non-invasive lesions that cannot be palpated. These are often smaller, of lower nuclear grade, and show much subtler changes than the lesions detected with less advanced mammographic equipment in the past. Technically good mammography requires exceptional attention to detail. The need for expert radiological interpretation cannot be overemphasised. The most common mammographic finding is microcalcifications, but some lesions may present as masses or architectural distortions with or without microcalcifications. Breast Magnetic resonance imaging (MRI) has been approved by the U.S. Food and Drug Administration (FDA) since 1991 for use as a supplemental tool, in addition to mammography, to help diagnose breast cancer. MRI is useful for staging breast cancer, determining the most appropriate treatment, and for patient follow-up after breast cancer treatment. Because MRI is more sensitive than mammography, it can help detect cancer that may be missed by mammography. However, because this increased sensitivity can also lead to false positive results, which requires breast biopsy procedures, the American Cancer Society does not recommend MRI for all women.
Neurotensin (NTS) is a 13 amino acids peptide formed from a large precursor, cleaved by convertases. NTS is commonly known for its distribution along the gastrointestinal tract. Typical physiological functions for NTS include stimulation of pancreatic and biliary secretions, inhibition of small bowel and gastric motility, and facilitation of fatty acids translocation. NTS was equally reported in functions linked specifically to neoplastic progression, including proliferation of the pancreas, prostate, colon, and lung cancer cells. We have previously described a potential role of NTS in breast tumor progression (Souaze et al (2006) Cancer Res. 66:6243-6249).
NTS peripheral functions are mediated through its interaction with NTSR1 (High affinity neurotensin receptor 1). When NTSR1 is challenged with NTS, phosphatidyl inositols are hydrolyzed leading to Ca2+ mobilization and PKC, ERK1/2, RhoGTPases, NFkappa-B, and focal adhesion kinase (FAK) activation.
Identifying patients with pathological initial stages but with a high risk of recurrence would be extremely useful, in order to individually tailor further management, in terms of more strict follow-up and/or adjuvant treatments.